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RAD001 for Patients With Radioiodine Refractory Thyroid Cancer

Primary Purpose

Thyroid Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
RAD001
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thyroid Cancer focused on measuring radioiodine refractory thyroid cancer, RAD001

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed locally advanced or metastatic thyroid cancer, excluding thyroid lymphomas not amenable to or refractory to surgical resection, external beam radiotherapy, radioiodine or other local therapies.
  • Prior therapy with chemotherapy and targeted therapies except for mTor inhibitors is allowed.
  • Medullary thyroid cancer with documented evidence of disease progression by modified RECIST within 6 months before study day 1 or symptomatic disease at the time of screening in the absence of documented disease progression.
  • Differentiated thyroid cancer with documented evidence of disease progression by modified RECIST within 6 months before study day 1.
  • Anaplastic thyroid cancer with disease progression with documented disease progression by modified RECIST within 6 months of study day 1.
  • Patients must have at least one measurable site of disease according to RECIST criteria that has not previously irradiated. If the patient has has previous radiation to the marker lesion(s), there must be evidence of progression since radiation.
  • 18 years of age or older
  • WHO performance status 2 or less
  • Adequate bone marrow, liver, and renal function
  • Fasting serum cholesterol 300mg/dL or less OR 7.75 mmol/L or less AND fasting triglycerides 2.5x ULN or less

Exclusion Criteria:

  • Patients receiving anticancer therapies within last 2 weeks or who have received radiation therapy within 3 weeks of study day 1
  • Prior therapy with mTOR inhibitors
  • Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study
  • Prior treatment with any investigational drug within the preceding 3 weeks
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
  • Patients should not receive immunization with attenuated live vaccines within 2 weeks of study entry or during study period
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • A known history of HIV seropositivity
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
  • Patients with an active, bleeding diathesis
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods
  • Patients who have received prior treatment wih an mTOR inhibitor
  • Patients with a known hypersensitivity to RAD001 or other rapamycins or to its excipients
  • History of noncompliance to medical regimens

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute
  • Mt. Sinai Medical Center
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm A

Arm Description

RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Median Progression Free Survival
Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Progression is measured using RECIST 1.1 criteria, defined as at least a 20% increase in size in target lesion and/or unequivocal progression of non-target lesions and/or appearance of new lesions. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free.

Secondary Outcome Measures

Objective Response Rate
The objective response rate is the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. PR or better is achieved if the following are true: Target Lesions: -At least a 30% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Non-target Lesions: No progression. No appearance new lesions or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Bone Lesions: ->50% increase in lesions. -No new lesions.
Median Overall Survival
Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.
Mean Change in Quality of Life [Medullary Thyroid Cancer Population Only]
The M. D. Anderson Symptom Inventory (MDASI) questionnaire was used to assess quality of life. Questions 1 to 19 were scored. Each of the 19 questions have a response range of 0 - 10, where 0 represents "not present" and 10 represents "as bad as you can imagine". The 19 responses are averaged together to create a mean score, with a lower score indicating a better quality of life. All questionnaire mean scores at each timepoint are averaged together to give a mean score at that timepoint (baseline and week 8) The mean change in quality of life is calculated by subtracting the baseline mean score from the week 8 mean score.

Full Information

First Posted
July 9, 2009
Last Updated
October 1, 2021
Sponsor
Dana-Farber Cancer Institute
Collaborators
Massachusetts General Hospital, M.D. Anderson Cancer Center, MOUNT SINAI HOSPITAL, Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00936858
Brief Title
RAD001 for Patients With Radioiodine Refractory Thyroid Cancer
Official Title
A Phase II Trial Using RAD001 for Patients With Radioiodine Refractory Thyroid Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
July 2009 (Actual)
Primary Completion Date
February 27, 2020 (Actual)
Study Completion Date
February 27, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Massachusetts General Hospital, M.D. Anderson Cancer Center, MOUNT SINAI HOSPITAL, Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Since thyroid cancer becomes refractory to radioactive iodine, treatment options are very limited. Tyrosine kinase inhibitors such as sorafenib have recently shown promise. This trial seeks to expand treatment options for this disease with a new, oral drug called RAD001. It is an inhibitor of the mTOR pathway and has shown activity in neuroendocrine cancers of the gastrointestinal tract and has been approved for the treatment of metastatic renal cell cancer.
Detailed Description
RAD001 will be taken once a day in the morning starting on Day 1 and continue until the participant is no longer participating in the study treatment. A history and physical exam will be performed the first day of the study and then once a month. Blood tests including coagulation studies, and thyroid studies will be performed monthly. A urine sample will need to be provided on the first day of treatment and then every 2 months. Imaging consisting of a CT or MRI of the neck, chest and abdomen will be done every 8 weeks after starting RAD001. Participants will remain on this research study for up to 24 months. However, if the participants doctor feels that they are benefiting from the study drug and they do not have severe side effects, they may be given the option to continue taking RAD001.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thyroid Cancer
Keywords
radioiodine refractory thyroid cancer, RAD001

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
RAD001
Other Intervention Name(s)
Afinitor (everolimus)
Primary Outcome Measure Information:
Title
Median Progression Free Survival
Description
Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Progression is measured using RECIST 1.1 criteria, defined as at least a 20% increase in size in target lesion and/or unequivocal progression of non-target lesions and/or appearance of new lesions. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free.
Time Frame
Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 48 months.
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
The objective response rate is the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. PR or better is achieved if the following are true: Target Lesions: -At least a 30% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Non-target Lesions: No progression. No appearance new lesions or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Bone Lesions: ->50% increase in lesions. -No new lesions.
Time Frame
Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 48 months.
Title
Median Overall Survival
Description
Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.
Time Frame
Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 5 years post study registration.
Title
Mean Change in Quality of Life [Medullary Thyroid Cancer Population Only]
Description
The M. D. Anderson Symptom Inventory (MDASI) questionnaire was used to assess quality of life. Questions 1 to 19 were scored. Each of the 19 questions have a response range of 0 - 10, where 0 represents "not present" and 10 represents "as bad as you can imagine". The 19 responses are averaged together to create a mean score, with a lower score indicating a better quality of life. All questionnaire mean scores at each timepoint are averaged together to give a mean score at that timepoint (baseline and week 8) The mean change in quality of life is calculated by subtracting the baseline mean score from the week 8 mean score.
Time Frame
Measured at baseline and then again at cycle 8 (8 months).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed locally advanced or metastatic thyroid cancer, excluding thyroid lymphomas not amenable to or refractory to surgical resection, external beam radiotherapy, radioiodine or other local therapies. Prior therapy with chemotherapy and targeted therapies except for mTor inhibitors is allowed. Medullary thyroid cancer with documented evidence of disease progression by modified RECIST within 6 months before study day 1 or symptomatic disease at the time of screening in the absence of documented disease progression. Differentiated thyroid cancer with documented evidence of disease progression by modified RECIST within 6 months before study day 1. Anaplastic thyroid cancer with disease progression with documented disease progression by modified RECIST within 6 months of study day 1. Patients must have at least one measurable site of disease according to RECIST criteria that has not previously irradiated. If the patient has has previous radiation to the marker lesion(s), there must be evidence of progression since radiation. 18 years of age or older WHO performance status 2 or less Adequate bone marrow, liver, and renal function Fasting serum cholesterol 300mg/dL or less OR 7.75 mmol/L or less AND fasting triglycerides 2.5x ULN or less Exclusion Criteria: Patients receiving anticancer therapies within last 2 weeks or who have received radiation therapy within 3 weeks of study day 1 Prior therapy with mTOR inhibitors Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study Prior treatment with any investigational drug within the preceding 3 weeks Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed. Patients should not receive immunization with attenuated live vaccines within 2 weeks of study entry or during study period Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study A known history of HIV seropositivity Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 Patients with an active, bleeding diathesis Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods Patients who have received prior treatment wih an mTOR inhibitor Patients with a known hypersensitivity to RAD001 or other rapamycins or to its excipients History of noncompliance to medical regimens
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Glenn Hanna, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Mt. Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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RAD001 for Patients With Radioiodine Refractory Thyroid Cancer

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